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Biochemical and estrogenic effects of Diuron and its metabolites, alone or in combination with alkylphenols in Nile Tilapia (Oreochromis niloticus)

Abstract

This project aims to elucidate some mechanisms of toxicity of diuron and three of its main metabolites (dichlorophenylurea, DCPU, dichlorophenylmethylurea, DCPMU and dichloroaniline, DCA), singly or in mixtures of diuron with its metabolites, and diuron and its metabolites with two environmentally relevant alkylphenois, nonylphenol (NP) and octylphenol (OP). Experiments will be performed by exposing Nile tilapias for 2 and 7 days to single compounds and in combination, and then a series of biochemical biomarkers will be evaluated: biotransformation enzymes (cytochrome P450 isoform 1A, glutathione S-transferase), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione reductase), levels of lipid peroxidation, reduced glutathione levels, quantification of micronuclei, and comet assays. To evaluate the estrogenic effect of diuron and its metabolites in combination with alkylphenois, it will be evaluated levels of testosterone, 11-ketotestosterone, 17 b-estradiol and vitellogenin in the plasma of fish, and activity of 17 b-hydroxy-steroid dehydrogenase and aromatase in the liver, in collaboration with Prof. Dr. Daniel Schlenk, from University of California (USA). Moreover, studies of in vitro and in vivo metabolism of the compounds by the fish will be carried out by measuring the presence of the compounds and their metabolites in plasma and bile of fish by U/HPLC coupled to a mass spectrometer, and incubation experiments of compounds with microsomal and cytosolic protein extracts and quantification of product formation by U/HPLC coupled to mass spectrometry. Similarly, the concentration of the compounds used in aquariums should be monitored. Studies of the inhibitory potential of compounds in the proposed enzymes will also be performed in vitro by incubating protein extracts of fish with increasing concentrations of the compounds and subsequent measurement of enzyme activity. We believe this project will bring a lot of new information regarding the mechanisms of action of diuron and alkylphenois in fish. In addition, this project will be also important in the establishment and consolidation of an international collaboration. (AU)

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FELICIO, ANDREIA ARANTES; FREITAS, JULIANE SILBERSCHMIDT; SCARIN, JESSICA BOLPETI; ONDEI, LUCIANA DE SOUZA; TERESA, FABRICIO BARRETO; SCHLENK, DANIEL; DE ALMEIDA, EDUARDO ALVES. Isolated and mixed effects of diuron and its metabolites on biotransformation enzymes and oxidative stress response of Nile tilapia (Oreochromis niloticus). ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, v. 149, p. 248-256, MAR 2018. Web of Science Citations: 5.
DE ALMEIDA, MILENA DEVECHI; BOSCOLO PEREIRA, THIAGO SCREMIN; BATLOUNI, SERGIO RICARDO; PEREIRA BOSCOLO, CAMILA NOMURA; DE ALMEIDA, EDUARDO ALVES. Estrogenic and anti-androgenic effects of the herbicide tebuthiuron in male Nile tilapia (Oreochromis niloticus). AQUATIC TOXICOLOGY, v. 194, p. 86-93, JAN 2018. Web of Science Citations: 5.
PEREIRA BOSCOLO, CAMILA NOMURA; BOSCOLO PEREIRA, THIAGO SCREMIN; BATALHAO, ISABELA GERTRUDES; ROSA DOURADO, PRISCILA LEOCADIA; SCHLENK, DANIEL; DE ALMEIDA, EDUARDO ALVES. Diuron metabolites act as endocrine disruptors and alter aggressive behavior in Nile tilapia (Oreochromis niloticus). Chemosphere, v. 191, p. 832-838, JAN 2018. Web of Science Citations: 12.
FELICIO, ANDREIA A.; CRAGO, JORDAN; MARYOUNG, LINDLEY A.; ALMEIDA, EDUARDO A.; SCHLENK, DANIEL. Effects of alkylphenols on the biotransformation of diuron and enzymes involved in the synthesis and clearance of sex steroids in juvenile male tilapia (Oreochromus mossambica). AQUATIC TOXICOLOGY, v. 180, p. 345-352, NOV 2016. Web of Science Citations: 4.
BOSCOLO PEREIRA, THIAGO SCREMIN; PEREIRA BOSCOLO, CAMILA NOMURA; FELICIO, ANDREIA ARANTES; BATLOUNI, SERGIO RICARDO; SCHLENK, DANIEL; DE ALMEIDA, EDUARDO ALVES. Estrogenic activities of diuron metabolites in female Nile tilapia (Oreochromis niloticus). Chemosphere, v. 146, p. 497-502, MAR 2016. Web of Science Citations: 11.
BOSCOLO PEREIRA, THIAGO SCREMIN; PEREIRA BOSCOLO, CAMILA NOMURA; HUMBERTO DA SILVA, DANILO GRUENIG; BATLOUNI, SERGIO RICARDO; SCHLENK, DANIEL; DE ALMEIDA, EDUARDO ALVES. Anti-androgenic activities of diuron and its metabolites in male Nile tilapia (Oreochromis niloticus). AQUATIC TOXICOLOGY, v. 164, p. 10-15, JUL 2015. Web of Science Citations: 14.

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